Excessive platelet aggregation leading to thrombosis and vascular occlusion causes a number of cardiovascular disorders including myocardial infarction and stroke. Extensive efforts have been made in the pharmaceutical industry to develop safe and effective anti-platelet drugs to prevent and treat these medical conditions. A major target in the development of new treatments of thrombotic vascular disorders is the integrin receptor ?II? 3. Existing orally-available ?II? 3 antagonists, developed with a goal of blocking the binding of fibrinogen to its receptor, have had disappointing results. These compounds interact with the open, active conformation of the receptor and maintain it in that form. Maintaining ?II? 3 in an open conformation results in essentially a constitutively active platelet, which may be detrimental to the survival of these cells. Therefore, one potential reason for the disappointing results of clinical studies with oral ?II? 3 antagonists may be that their maintenance of continued ?II? 3 signaling could counter the therapeutic effects of blocking fibrinogen binding. Developing allosteric inhibitors that could maintain ?II? 3 in an inactivate conformation would prevent fibrinogen binding, thereby blocking thrombosis but also prevent ?II? 3 signaling possibly overcoming the problems associated with available ?II? 3 antagonists. Encode Bio has developed an optical technology which can be employed to measure conformational changes in proteins from inactive to active states in a high throughput manner without the drawbacks found in other biophysical techniques. Encode Bio proposes to develop a drug screening assay (based on its optical technology) which can be employed to identify allosteric inhibitors of the integrin receptor ?II? 3. PUBLIC HEALTH RELEVANCE: The increasing mortality associated with thrombosis has led to the development of a number of drugs to reduce platelet aggregation for treatment of thrombotic vascular disease. A major focus of recent anti- thrombosis drug development has been inhibitors of the integrin receptor ?II? 3. Identifying allosteric inhibitors that selectively bind to the inactive conformation of this integrin receptor could yield more effective antagonists than presently available. To discover allosteric inhibitors, one would need to have a way to measure the inactive conformation of the receptor and detect its shift to an active form. Encode Bio proposes to develop a drug screening assay which can be employed to identify allosteric inhibitors of the integrin receptor ?II? 3.